Daily or circadian rhythms which occur in man and most other organisms have a significant functional importance and represent a fundamental property at the cellular level. It is the objective of the proposed research to study and delineate the cellular and molecular phenomena which are involved in these circadian biological rhythms and to understand the mechanism responsible. The research will utilize: (1) a unicellular dinoflagellate (Gonyaulax) for which there is already a considerable amount of background data and (2) human red blood cells. (1) It is proposed that the circadian clock is the same as the cell cycle, the cellular mechanism ultimately responsible for cell division. Experiments to test this idea involve showing that even when circadian cells are dividing slowly, they experience multiple cell cycle rounds and that a cell cycle with a different frequency is not involved. (2) Several different biochemical correlates, which in effect are markers of the circadian cycle are already known in Gonyaulax and in some mammalian cells as well. Activities vary, sometimes by as much as a factor of 10, over the course of a cycle. The cause of this variation will be studied and should allow us to specify the underlying mechanism. (3) The in vivo circadian rhythm will be studied and analyzed by the use of specific drugs, inhibitors, membrane active agents, and also by following rhythmicity in single isolated cells. (4) Circadian rhythms in isolated human red blood cells have recently been reported. This phenomenon will be confirmed and the mechanism elucidated. Analysis of the properties of biological rhythms reveal much in common from man to microorganism indicating similarities in functions and in mechanism. The proposed study can thus be expected to provide information relevant to our understanding of rhythms in man.